Delta 9-tetrahydrocannabinol (Delta 9-THC) is the major psychoactive component of marihuana. This drug has been shown to inhibit cellular macromolecular synthesis and to have suppressive effects on the host immune system. It has been shown, also, to decrease host resistance to Herpes simplex virus types 2 (HSV2) in the mouse. The increased use of marihuana among individuals who may be at risk of developing herpes genitalis, presents the hazard of decreased host resistance to this venereal disease. The goal of this research is to define the process by which Delta 9-THC induces decreased resistance of HSV2 genital infection in the guinea pig. The guinea pig has been selected as the animal of choice for these studies since HSV2 induces a spectrum of clinical disease similar to that seen in humans. It is proposed to determine the dose response curve for Delta 9-THC for decreased resistance to HSV2 using expression of lesions, virus shedding, and mortality as the response. The interval of susceptibility for decreased resistance will be established. Using a Delta 9-THC dose which produces a 50-80% increase in susceptibility to HSV2 genital infection, guinea pig serum will be tested for deficiency in ability to abrogate HSV2 infection in terms of interferon induction, virus-specific IgM and IgG responses, and complement levels. Host immunocompetent cells, such as peripheral blood lymphocytes, spleen cells, and peritoneal exudate cells will be tested for deficiency in B-cell, T-cell, and macrophage response to HSV2. Cells which function in nonspecific host resistance will also be examined. The direct effect of Delta 9-THC on virus protein synthesis, DNA synthesis, and replication will be assessed. In addition, a guinea pig model of HSV2 latent infection will be developed to allow for studies on the effect of Delta 9-THC on recurrent infection.